Human skin, like all other organs, undergoes chronological and biological aging. In addition, unlike other organs, skin is in direct contact with the environmental factors, thus further contributing to premature aging. Age-related changes in elderly skin include clinical, histological, and biochemical changes. The clinical effects of aging on the skin are common to all humans and are characterized by wrinkles, dry and thinning skin and volume loss. Aside from the visible effects of aging, aging has a psychological impact in individuals by reducing self-esteem or even causing others to misjudge the competency of individuals.
The development of signs of skin aging has traditionally been considered as due to both intrinsic and extrinsic factors. Intrinsic factors refer to structural, biochemical, and physiological changes that occur as a natural consequence of aging and are considered genetically determined. Intrinsic aging is also called chronologic or “natural” aging. Extrinsic factors include environmental factors such as smoking, alcohol consumption, air pollution, ultraviolet exposure and stress. Of all extrinsic causes, UV radiation from sunlight has the most widespread documentation of its negative effects on the skin and thus is considered as the most important extrinsic factor as it relates to skin aging. Because of this, extrinsic aging is often referred to as photoaging.
Even without extrinsic factors such as stress or exposure to UV light, skin starts to begin the inherent process of aging around an individual's mid-twenties as the productions of collagen and elastic fibers decline. All layers of skin (epidermis, dermis, dermal connective tissue and subcutaneous fat) atrophy over time with skin, while skin becomes increasingly dehydrated to due to increased transepidermal water loss in increasingly atrophic skin. Elastin provides much of the elastic recoil properties of skin, arteries, lungs, and ligaments. Loss of elastin is a major part of what causes visible signs of aging (wrinkles, sagging) in skin. Eighty percent of the dry weight of skin is reported to be collagen, responsible for the tensile strength of skin.
Intrinsic and extrinsic factors do not operate exclusively and independently of each other. The intrinsic rate of skin aging in any individual can be dramatically influenced by environmental factors, such as with the amount of exposure to UV radiation and overall stress experienced by the individual. With increasing UV exposure as well as stress, skin's ability to repair itself is diminished.
Telomeres, repetitive and protective nucleotide regions that help prevent chromosome degradation, are known to be linked to aging, cancer, and death. These regions at the ends of chromosomes help protect genomic integrity by acting as a buffer during the inevitable degradation of the end of DNA strands during cellular division. In addition to the inevitable degradation caused during DNA replication, telomeres have been shown to be highly susceptible to damage from oxidative stress. Telomeres shorten over time and eventually the accumulated damage results in non-dividing cells, cellular senescence, and apoptosis. This molecular and cellular process produces the effects of aging: muscles weaken, eyesight and hearing fade, organs fail, and with respect to the skin, cutaneous signs of aging such as wrinkles. Counteracting the continued loss (shortening) of telomeres are enzymes called telomerase. This protein adds nucleotide repeats at to the 3′ end of DNA strands, which delays the eventually effects of telomeric shortening. However, telomerase levels naturally decline with age.
UV light, whether from the sun or other sources, breaks down collagen and impairs the skin's ability to create new collagen. UV light also damages elastic fibers, cross-linked glycoproteins which are produced by fibroblasts in the extracellular matrix of skin, and which impart elasticity to skin. Similarly, stress-induced release of cortisol has been linked to collagen loss in skin. Stress also adds to the natural intrinsic loss of telomeres by directly altering telomere dynamics, causing attrition and hindering restoration of chromosomal length.
The current and traditional understanding of skin aging (i.e. extrinsic vs. intrinsic) factors is too generalized. This invention is a novel multi-tiered conceptual approach to skin aging based on DNA (genomic), environmental, hormonal, and cellular and physiologic and etiologic factors implicated and observed in aging skin. The suggested composition of the present invention has been specifically selected to address these factors.
Referencing FIG. 1, a number of etiological factors lead to consequence ultimately resulting in aged skin. The etiological factors are epigenetic, environmental, hormonal, and cellular. Methylation of DNA relates the epigenetic factor. UV light and stress are environmental factors. DHEA is a hormonal factor. These lead to consequences. The consequences include cellular and histological consequences such as reduction in collagen, elastin fibers, glycosaminoglycans (GAGs), skin moisture. Clinical cutaneous consequences include thinning, loss of elasticity, and dryness. The resulting feature of all of these factors is the appearance of aged skin.
Epigenetic factors play a vital and essential role in cutaneous aging. Epigenetics is the underpinning of the other factors. Epigenetics refers to changes in genes expression resulting without changes in the underlying DNA sequence. Unlike genetic mutations, which can take generations to result in functional changes in gene expression, epigenetic changes in gene expression can result from a single “stress” event within an individual's lifetime and can have profound consequences within a matter of days.
Epigenetic changes in gene expression occur primarily through changes in DNA methylation and chromatic structure. Methylation is the process of adding one or more methyl groups onto a nucleotide sequence. This a common signaling tool that cells use to lock genes in the “off” position and to perform DNA repair. Methylation is a biochemical process that is essential for the proper function of almost every physiologic system in the body.
Authorities consider enhancement of methylation as critical in protecting against many diseased states, including cancer, liver disease, and neurological disorders. With respect to aging, there is a global and continued loss of DNA, consistent with the notion that DNA methylation is in fact a dynamic and ongoing process. Furthermore, environmental factors appear to directly impact epigenetic mechanisms such as DNA methylation. Lending support to this notion is a longitudinal study of twin children which indicated that there was a documented divergence of methylation patterns among twin children due to environmental factors who were separated for several years from each other. Other factors that decrease methylation include smoking, alcohol consumption, high fat diets, birth control pills, and aging itself.
Given the central and critical role of methylation in chromosomal stability which underlies all physiologic activities and biochemical reactions, including the ongoing hypomethylation that appears directly related to aging, the inventor points out that DNA methylation also affects the transcription and translation of DNA and RNA encoding for vital skin structures such as collagen, elastin, and enzymes such as collagenase and elastase. For these reasons, the inventor has found an important role and need for a natural molecule that can enhance DNA methylation in the proposed anti-aging skin formulation.
Many different treatments have been suggested to decrease the signs of aging. Many current oral and topical treatments known in the prior art focus on very narrow aspects of the dermatological effects of skin aging, such as collagen and elastic fibers, UV protection, or antioxidants. Cosmetic procedures such as chemical peels, radiofrequency, or laser treatments can help to increase the production of collagen, and/or elastic fibers, but these represent a rather narrow focus of treatment. They do not address the plurality of factors, including genetic factors, clinical and environmental factors, hormonal changes, and complex cellular and physiologic changes that are implicated in and observed in skin aging. Furthermore, many of these treatments are expensive and are not options for all individuals, especially since the treatments may cause pigmentation lose that would be more obvious on darker skin tones. Similarly, injections of foreign material such as calcium hydroxylapatite and cross-linked hyaluronic acid focus solely on filling and adding volume to the deep dermal or subcutaneous tissue, and are also limited in their scope of therapy and therapeutic benefits. Such injections typically last for up to 2 years and require repeated re-injections. Finally surgical treatments such as face lifts focus on purely aesthetic considerations (tightening loosening skin) and carry their own inherent risks associated with surgical procedures.
There is a need to have a single effective composition that helps to address a plurality of factors of skin aging as described below and that does not require surgery, injections, or topical and oral preparations that merely mitigate against a narrow scope of causes of skin aging.
The present invention is unique in several respects. It is the only product ever formulated based on a novel multi-tiered understanding that reflects both etiologic factors as well as end-result changes (consequences) observed histologically in the tissue of aged skin. The composition recognizes and highlights the basic and vital role of epigenetics, specifically DNA methylation, in skin aging. As such, it is the only known formulation geared towards ameliorating signs of skin aging that specifically incorporates folic acid and trimethyglycine as potent DNA methylators. Next the formulation addresses the vital role of environmental factors such as stress which can in turn also affect how our DNA methylates. Once the different etiologic factors (genomic, clinical, hormonal, and cellular) are addressed, the formulation addresses the observed cellular and histologic changes in skin. The final end result or goal of this composition addresses all of the necessary underlying etiologic and physiologic/cellular observed changes. To that end 14 natural molecules that work synergistically together to address all the factors described above have been included.
Given the interdependency of the factors listed above, as well as the mechanisms of actions of the fourteen molecules, there is no need for any one component to be maximally dosed in order to achieve its limited scope of benefits. For instance, rather than using the maximal or high doses of Vitamin C (as found in Camu Camu) to increase collagen synthesis, collagenase inhibitor white tea extract is included in order to reduce the ongoing loss of collagen by this enzyme. Thus, lower doses of Vitamin C can be included for this specific purpose. Furthermore, given the invariably interlocked mechanisms of cellular aging addressed in the formulation, improvement in one factor (such as healthier elastic fibers) can have a corresponding positive impact on another factor (less overall elastase released by the body).